PMID- 23708521
OWN - NLM
STAT- MEDLINE
DCOM- 20140204
LR  - 20211021
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 12
IP  - 12
DP  - 2013 Jun 15
TI  - Intermittent injections of osteocalcin reverse autophagic dysfunction and 
      endoplasmic reticulum stress resulting from diet-induced obesity in the vascular 
      tissue via the NFkappaB-p65-dependent mechanism.
PG  - 1901-13
LID - 10.4161/cc.24929 [doi]
AB  - The osteoblast-specific secreted molecule osteocalcin behaves as a 
      hormone-regulating glucose and lipid metabolism, but the role of osteocalcin in 
      cardiovascular disease (CVD) is not fully understood. In the present study, we 
      investigated the effect of osteocalcin on autophagy and endoplasmic reticulum 
      (ER) stress secondary to diet-induced obesity in the vascular tissue of mice and 
      in vascular cell models and clarified the intracellular events responsible for 
      osteocalcin-mediated effects. The evidences showed that intermittent injections 
      of osteocalcin in mice fed the high-fat diet were associated with a reduced body 
      weight gain, decreased blood glucose and improved insulin sensitivity compared 
      with mice fed the high-fat diet receiving vehicle. Simultaneously, the 
      administration of osteocalcin not only attenuated autophagy and ER stress but 
      also rescued impaired insulin signaling in vascular tissues of mice fed a 
      high-fat diet. Consistent with these results in vivo, the addition of osteocalcin 
      reversed autophagy and ER stress and restored defective insulin sensitivity in 
      vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) in the 
      presence of tunicamycin or in knockout XBP-1 (a transcription factor which 
      mediates ER stress response) cells or in Atg7(-/-) cells. The protective effects 
      of osteocalcin were nullified by suppression of Akt, mammalian target of 
      rapamycin (mTOR) or nuclear factor kappa B (NFkappaB), suggesting that osteocalcin 
      inhibits autophagy, ER stress and improves insulin signaling in the vascular 
      tissue and cells under insulin resistance in a NFkappaB-dependent manner, which may 
      be a promising therapeutic strategies of cardiovascular dysfunction secondary to 
      obesity.
FAU - Zhou, Bo
AU  - Zhou B
AD  - Key Laboratory of Environment and Genes Related to Diseases, Ministry of 
      Education, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Li, Huixia
AU  - Li H
FAU - Liu, Jiali
AU  - Liu J
FAU - Xu, Lin
AU  - Xu L
FAU - Zang, Weijin
AU  - Zang W
FAU - Wu, Shufang
AU  - Wu S
FAU - Sun, Hongzhi
AU  - Sun H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130520
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (NF-kappa B)
RN  - 104982-03-8 (Osteocalcin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects/genetics
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Diet, High-Fat/adverse effects
MH  - Endoplasmic Reticulum Stress/*drug effects/genetics
MH  - Gene Silencing
MH  - In Vitro Techniques
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron
MH  - NF-kappa B/genetics/*metabolism
MH  - Obesity/chemically induced/genetics/*metabolism
MH  - Osteocalcin/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC3735704
OTO - NOTNLM
OT  - Akt
OT  - ER stress
OT  - NFkappaB
OT  - autophagy
OT  - mTOR
OT  - obesity
OT  - osteocalcin
EDAT- 2013/05/28 06:00
MHDA- 2014/02/05 06:00
PMCR- 2014/06/15
CRDT- 2013/05/28 06:00
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2014/02/05 06:00 [medline]
PHST- 2014/06/15 00:00 [pmc-release]
AID - 24929 [pii]
AID - 2013CC4917R [pii]
AID - 10.4161/cc.24929 [doi]
PST - ppublish
SO  - Cell Cycle. 2013 Jun 15;12(12):1901-13. doi: 10.4161/cc.24929. Epub 2013 May 20.